The Neuropathology Core will continue to play a vital role in the ongoing Program. The Neuropathology Core serves to obtain autopsy-derived brain specimens from individuals who have been evaluated and followed longitudinally by the Clinical Core especially residents of the Jewish Home and Hospital for the Aged, a very large academically affiliated nursing home. We strive to obtain the brain specimens with the shortest post-mortem interval and for the entire specimen collection the mean postmortem interval is less than 6 hours. The specimens are dissected and preserved in a manner that maximizes their utility for the needs of both the proposed experiments within the Program as well as other research projects within the Mount Sinai ADRC as well as independent aging-related projects. This includes snap freezing one half of the brain specimen and fixing the other half is freshly prepared paraformaldehyde. The dissection protocol in place allows for the preparation of selected regions of the brain in such a way that the non-biased sampling techniques of stereology can be applied to quantify lesion and neuron numbers. A detailed neuropathologic workup is carried out to establish a neuropathologic diagnosis as well as to document the extent and distribution of relevant neuropathologic lesions. These data are entered into an extensive data base which can be integrated into the clinical data base for the purpose cliniconeuropathologic correlative investigations. The Neuropathology Core will also provide assistance and expertise in the morphologic evaluation of newly developed transgenic animals as well as those transgenic animals exposed to experimental manipulations. We will interpret the nature of any identified lesions for their relevance as models of AD or other human neurodegenerative conditions. Because this Brain Bank has been operating for approximately 18 years, an efficient and effective operating structure for the Brain Bank already exists. The tissues we have collected have been extensively used in a wide range of studies. They are extensively requested both by researchers within the ADRC, the greater Mount Sinai research community and by many other investigators throughout the US and even internationally. The overall aim of this core is to continue to maintain and operate the Brain Bank in such a way as to meet the needs of the cores and studies in the ADRC in an optimal fashion.